Modulation of free intracellular calcium and cAMP by morphine and cannabinoids, alone and in combination in mouse brain and spinal cord synaptosomes.

Department of Pharmacology and Toxicology, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298-0613.

Abstract

Changes in [Ca++]i and cAMP were evaluated as possible mechanisms by which the cannabinoids enhance the antinociception of morphine. The addition of subactive concentrations of delta 9-(THC) and morphine in combination to brain synaptosomes did not result in an enhanced decrease in [Ca++]i; however, this drug combination enhanced decreases in [Ca++]i in spinal cord synaptosomes. The combination of CP55,940 and morphine produced enhanced decreases in [Ca++]i in both brain and spinal cord synaptosomes. In brain synaptosomes, the combination of delta 9-THC and morphine produced an additive decrease in cAMP accumulation, whereas no significant change was observed with this combination in the spinal cord. Thus, the difference in the modulation of [Ca++]i but not cAMP in the brain in vitro may be a predictor of the greater-than-additive antinociceptive effects observe in vivo.